Abbott's Absorb bioresorbable stent
Ongoing clinical trials of bioresorbable stents continue to show positive data for the devices, which are widely expected to overtake metallic stents in the coming years if the data trend continues. One of the most important news items from the late-breaking sessions at the 2014 Transcatheter Cardiovascular Therapeutics (TCT) meeting last fall were the one-year results from the ABSORB II trial. It is the world's first prospective, randomized, controlled trial comparing the safety and effectiveness of the Abbott’s bioresorbable Absorb Bioresorbable Vascular Scaffold (BVS) drug-eluting coronary stent to Abbott's market-leading metallic Xience family of drug eluting stents (DES). The trial included 501 patients and was conducted primarily in Europe.
At one year, the clinical outcomes were the same, but the bioresorbable stent patients reported a significantly lower incidence of angina or the need for nitrates to alleviate chest pain. This opens up an entirely new avenue of research into these devices and their potential benefits. This finding also inspired changes in the upcoming ABSORB IV trial to examine angina outcomes specifically.
“There was no difference in safety, which is something we wanted to see if there was any difference in stent thrombosis and there was no difference in target lesion revascularization or restenosis,” said Jim Hermiller, M.D., FACC, director of interventional cardiology, St. Vincent Heart Center, Indianapolis, and a principle investigator of the ABSORB III Trial.
He said there was a question of whether the thicker stent struts on the bioresorbable stents would increase stent thrombosis or other complications, but no adverse effects were observed when compared to conventional metallic DES.
Reduced Chest Pain
Chest pain has a significant impact on a patient’s quality of life and it is a cost burden on the healthcare systems, since cardiac patients with chest pain frequently go to the emergency department for immediate evaluation. New data suggesting bioresorbable stents may reduce or eliminate chest pain post-percutaneous coronary intervention (PCI) was a major finding in the trial.
“There is a substantial difference in the frequency in which people had angina and needed to be readmitted to the hospital for revascularization due to chest pain in the metallic DES patients,” Hermiller said. “It’s very expensive if a patient comes back after PCI with chest pain. There is a high frequency of recatheterization, stress testing and going through another hospital readmission. It really does impact the quality of life of these patients.”
No one is sure why patients felt less angina, so this is something that will be examined closely in upcoming trials.
“The BVS is a very flexible device, so you don’t straighten out the coronaries like you do with a metallic stent,” Hermiller explained. “There are other hypotheses that maybe there is less neurogenic injury of the nerves that run in the adventitia of these vessels.”
Future Use of Bioresorbable Stents
Two bioresorbable stents are now cleared for clinical use in Europe and Abbott’s Absorb BVS is currently involved in the ABSORB III U.S. Food and Drug Adminsitration (FDA) pivotal trial, the first U.S. trial for a bioresorbable stent. While data from trials abroad have been very positive, thought interventional cardiology leaders are cautious about making broad endorsement of these devices until they have more data. Chiefly, they want to see more clinical data on their use in more complex lesions, rather than the simpler, straightforward lesions that have been included in trials so far. Durability of vessel outcomes is also being watched closely to determine what happens to patients after the stent dissolves years after implant.
“The big question is long-term durability,” Hermiller said. “With metallic stents there are long-term problems of having a permanent metallic implant in the vessel wall.”
So far, experience has shown as the resorbable stent dissolves, the vessels return to a normal state, allowing vasoconstriction and dilation.
“It certainly seems better for the vessel not to have this cage in it forever,” Hermiller said. “And we also see long-term that the vessels tend to have positive remodeling where they get bigger and there tends to be a very unreactive neointimal that forms. So, there are lots of signals that this is going to be very helpful down the road, and as a consequence I think we are going to move to this technology. In the future, I think this will be the platform on which we do everything we do.”
ABSORB II Data
"The results of ABSORB II provide international doctors with additional confidence to use Absorb to treat their patients based on randomized clinical data showing that Absorb provides comparable results at one year to a best-in-class metallic drug eluting stent in traditional endpoints," said Patrick Serruys, M.D., Ph.D., professor of interventional cardiology at the Thoraxcentre, Erasmus University Hospital, Rotterdam, the Netherlands, and principal investigator of the ABSORB II trial. "Additionally, the lower rate of chest pain observed in people treated with Absorb is a promising finding that shows that Absorb may offer people unique quality of life benefits beyond the excellent clinical outcomes already offered with drug-eluting stents."
At one year, the patient-oriented clinical endpoint of all death, all heart attacks and all revascularization was 7.3 percent for Absorb and 9.1 percent for Xience (p=0.47). The device-oriented clinical endpoint of target lesion failure (TLF) was 4.8 percent for Absorb and 3 percent for Xience (p=0.35) at one year. The individual components of these composite endpoints were also comparable between the two treatment groups. The rates of stent thrombosis (ST) observed for Absorb at one year were low at 0.6 percent for definite ST and 0.9 percent for definite/probable ST.
The data also showed that during the course of one year, people treated with Absorb were less likely to experience angina once they left the hospital than those treated with Xience, at a rate of 16.4 percent versus 25.6 percent (p=0.01), respectively. Angina occurs when there is not enough oxygen-rich blood flowing to the heart muscle. Angina has a significant impact on quality of life and healthcare costs. Overall, people who have angina following a heart stent procedure use more healthcare resources, including additional diagnostic and treatment tools to try to identify the source of angina, than those without angina. In addition, they typically have a lower quality of life because they are less likely to lead active lifestyles than those people without angina. Therefore, reducing the burden of angina could help people live healthier lives and reduce costs to the healthcare system.
The primary endpoint of the ABSORB II trial is vessel motion at three years, at which time Absorb has fully dissolved. Without a permanent stent caging the vessel, the vessel has the potential to return to a more natural state. Clinical endpoints and quality of life measures will be assessed annually for up to three years. Imaging endpoints, or specialized pictures inside the blood vessel, will be assessed at three years.
ABSORB IV Trial
Abbott announced the start of the ABSORB IV clinical trial in October, which will test whether the Absorb is more cost effective and offers a higher quality of life than the Xience metallic DES. The trial is designed to enroll approximately 3,000 people with coronary artery disease, mostly in the United States.
ABSORB IV is the first randomized heart stent trial to prospectively measure angina as a primary endpoint at one year. Measuring angina is significant because of its impact on quality of life and healthcare costs. Overall, people who have angina following a PCI use more healthcare resources than those without angina. Studies have shown that while PCI with metallic stents is highly effective by reducing angina for 75 percent of treated patients, about 25 percent of people treated still experience angina over the course of the year following PCI. In addition, people with frequent angina typically have a lower quality of life because they are less likely to lead active lifestyles than those without angina.
The other primary endpoint of ABSORB IV assesses long-term clinical safety and performance based on the change in target lesion failure (TLF) from one to five years. TLF is a traditional endpoint in heart stent trials used to measure the safety and effectiveness of a device. It is designed to demonstrate that this performance is consistent out to five years in people treated in the United States.